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Biomedical subjects

F Lejeune

Publications and source records attributed to F Lejeune.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and cytotoxic properties of new N-substituted 4-aminophenol derivatives with a potential as antimelanoma agents.

New tyrosinase-targeted compounds based on structural variants of the prototype unit 4-aminophenol have been synthesized and screened for their potential as antitumour agents against malignant melanoma. Cytotoxicity assays showed that N-4-hydroxyphenylglycine (NHPG) and its alpha-methyl derivatives methylphenylglycine and dimethylphenylglycine exhibit significant antiproliferative effects on pigmented human melanoma cell lines (HBL), with inhibitory concentrations at 50% (IC50) around 80 micrograms/ml. A marked increase in cytotoxicity was observed with morpholine-containing 4-aminophenols, e.g. N-(2-morpholinoethyl)-4-aminophenol, which showed an IC50 of 20 micrograms/ml of HBL cells. Much more pronounced was the effect of the diacetoxy-derivative, DiAcMoAc, which showed an IC50 of 15 micrograms/ml on HBL cells and as low as 2 micrograms/ml on tyrosinase-containing, non-pigmented human melanoma cells (LND1), with a toxicity response of the same order of magnitude as that of melphalan. These results open interesting perspectives in the design of new targeted pro-drugs against malignant melanoma.

Aminophenols↗
PubMed1992

Neonatal treatment of giant naevi.

A technique of curettage of giant congenital naevi in newborns was proposed by Moss in 1987. We used this technique in 6 children during the last 2 years. The long-term aesthetic results appear to be better than those observed after other methods of treatment. Light microscopy of the pigmented skin confirmed the presence of the majority of naevus cells in the upper dermis. For 3 patients, cultures of the curetted cells showed a melanocyte behaviour similar to that seen in malignant melanoma. These observations are limited to in vitro cultures and are not representative of the in vivo evolution as biopsies of the remaining naevus cells at 3 months of age did not show any malignant characteristics.

Curettage↗
PubMed1992

S 14671: a naphtylpiperazine 5-hydroxytryptamine1A agonist of exceptional potency and high efficacy possessing antagonist activity at 5-hydroxytryptamine1C/2 receptors.

The interaction at 5-hydroxytryptamine (5-HT) receptors of the novel naphtylpiperazine, S 14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine), was compared to that of the 5-HT1A ligands, 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), WY 50,324 [N-(29(4-(2-pyrimidinyl)-1-piperazinyl)ethyl)tricyclo(3.3.1.1(3,7) )- decane-1-carboxamide], (+)-flesinoxan, buspirone and BMY 7378 [(8-[2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl]-8-azaspirol[-4-]-decane-7,9-dione 2HCl]. S 14671 showed a very high affinity for 5-HT1A sites (pKi, 9.3) as compared to the reference ligands (pKi values, 9.2, 8.7, 8.7, 7.9 and 8.7, respectively). S 14671 bound in an apparently competitive manner and, in distinction to the reference compounds, possessed a Hill Coefficient (1.4) significantly superior to 1. Although showing low affinity at 5-HT1B and 5-HT3 sites, S 14671 displayed significant affinity at both 5-HT1C and 5-HT2 sites; pKi, 7.8 in each case. Furthermore, S 14671 acted as an antagonist of 5-HT-stimulated phosphoinositide turnover in rat choroid plexus (5-HT1C) and cortex (5-HT2). In vivo, upon s.c. administration, S 14671 acted as a high efficacy agonist in models of 5-HT1A receptor-mediated activity: induction of flat-body posture, spontaneous tail-flicks, hypothermia and corticosterone secretion and inhibition of morphine-induced antinociception. In every test, S 14671 was the most potent compound: it was active at doses as low as 5 micrograms/kg s.c. Relative potency across all tests was S 14671 greater than 8-OH-DPAT greater than WY 50,324 greater than (+)-flesinoxan greater than buspirone with BMY 7378 too weak for comparison to be meaningful. The action of S 14671 in 5-HT1A tests was blocked by BMY 7378 and the 5-HT1A antagonist, (-)-alprenolol, but unaffected by the 5-HT1C/2 antagonist, ritanserin, and the 5-HT3 antagonist, ondansetron. Activation of postsynaptic 5-HT1A receptors was confirmed in 5,7-dihydroxytryptamine-lesioned rats, in which the potency of S 14671 to elicit spontaneous tail-flicks was potentiated. Activation of presynaptic receptors was demonstrated by inhibition of the electrical activity of the dorsal raphe nucleus with the following order of relative potency: S 14671 greater than 8-OH-DPAT greater than WY 50,324 greater than BMY 7378 greater than buspirone. Spiperone, which acts as a pure 5-HT1A antagonist at raphe 5-HT1A receptors, blocked the action of S 14671. In conclusion, S 14671 is a structurally novel ligand manifesting high efficacy and exceptional potency at both pre- and postsynaptic 5-HT1A receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

S 14671: a novel naphthylpiperazine 5-HT1A agonist of high efficacy and exceptional in vivo potency.

The novel, naphthylpiperazine 5-HT1A agonist, S 14671 (4-[(thenoyl-2)aminoethyl]-1-(7-methoxynaphtylpiperazine], displayed very high affinity for 5-HT1A binding sites (pKi = 9.3) as compared to the serotonin (5-HT)1A agonists, 8-OH-DPAT (9.2) and (+)-flesinoxan (8.7) and the 5-HT1A partial agonists, buspirone (7.9) and BMY 7378 (8.8). In vivo, S 14671 induced the typical 5-HT1A agonist-induced responses of hypothermia and spontaneous tail-flicks at doses as low as greater than or equal to 5 micrograms/kg s.c. and greater than or equal to 40 micrograms/kg s.c., respectively. In each test, it was about 10-fold more potent than 8-OH-DPAT and 100-fold more potent than (+)-flesinoxan and buspirone. The actions of S 14671 could be blocked by BMY 7378 and the 5-HT1A receptor antagonist, (-)-alprenolol, but not by the 5-HT1C/2 receptor antagonist, ritanserin, nor the 5-HT3 receptor antagonist, ICS 205930. Thus, S 14671 is a novel 5-HT1A ligand of high efficacy and exceptional in vivo potency.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Degradation of alpha-melanocyte stimulating hormone (alpha-MSH) by CALLA/endopeptidase 24.11 expressed by human melanoma cells in culture.

The common acute lymphoblastic leukemia antigen (CALLA) is identical to human endopeptidase 24.11 (E-24.11) and is expressed on certain human melanoma lines. This work was conducted in order to investigate whether alpha-melanocyte-stimulating hormone (alpha-MSH) could be a substrate for E-24.11, its degradation leading to the negative alpha-MSH radiobinding assay results observed with some CALLA-positive cell lines. We used 3 human melanoma cell lines (GLL-19, Mel Juso and G361) which lack receptors to alpha-MSH and express CALLA, and, as a control, one CALLA-negative melanoma cell line (HBL) with specific receptors for alpha-MSH. Radioimmunoassays give evidence that alpha-MSH was degraded in the presence of the 4 melanoma cell lines and that disappearance of the peptide was significantly reduced by phosphoramidon in 2 lines (GLL-19 and G361). Upon incubation of alpha-MSH with GLL-19 and G361 cell membranes, 3 degradation products were completely abolished in the presence of phosphoramidon. Amino acid content analysis of alpha-MSH fragments produced by purified E-24.11 permitted identification of 6 peptide bonds in the sequence of alpha-MSH susceptible to cleavage by the enzyme. It is concluded that alpha-MSH is a substrate in vitro for purified E-24.11 and for the enzyme present on the human melanoma cell lines GLL-19 and G361, expressing a high level of endopeptidase activity. However, hydrolysis of alpha-MSH by this enzyme does not seem to represent the main factor responsible for the apparent absence of receptors for the hormone on some cell lines.

Amino Acid Sequence↗
PubMed1989

Upper extremity function after conservative interscapulo-thoracic tumor resection.

Six patients who had undergone an en bloc interscapulo-thoracic excision (for primary bone or soft tissue sarcoma in five, and metastatic disease in one) were subject to review, with special emphasis on the functional outcome of the operated arm. Active shoulder motion was poor in all patients, but this did not prevent passive positioning of the hand and elbow. Elbow and particularly hand function was either not, or only slightly, impaired so that two patients regained full use of their upper extremity. Three patients had satisfactory but impaired function and one with metastatic disease of the should had a poor functional outcome.

Adult↗
PubMed1989

Surgical treatment of bone metastases of the peripheral skeleton--a review of 33 cases.

Out of a total of 31 patients (26 females and five males) there were 24 complete and nine impending pathological fractures. These, treated from October 1985 to September 1987 at the Bordet Institute, were evaluated. Breast cancer was the most frequent underlying disease (66%) followed by lung cancer (12%). Eighteen lesions were treated by endoprosthetic replacement and 15 by an intramedullary fixation device. Bone cement was added to either of these. Satisfactory pain relief was obtained in 82% of the treated areas and restoration of function in 76%. Complications were rare but included one easily resolved superficial wound infection, four deep venous thromboses, movement limited to 21% (seven joints), and the changing of two fixation or reconstruction devices. Median survival time was 6 months; 35% of the patients were still alive after 12 months and 10% after 24 months.

Adult↗
PubMed1988

[Electrophysiological study of tianeptine, a new enhancer of serotonin uptake with antidepressant activity].

Tianeptine is a clinically effective antidepressant, not chemically related to classical tricyclic compounds. Its mechanism of action preferentially involves central serotoninergic transmissions, by increasing uptake after acute and chronic administration in rat brain and platelets and in human platelets. We studied the effects of tianeptine on three currently used electrophysiological methods: Ro4-1284 induced PGO waves in the cat, neocortical EEG activity in the acute rat preparation and sleep-wakefulness modifications in chronically implanted rats. Density of Ro4-1284 induced PGO waves was reduced by tianeptine, the minimal effective dose being 2 mg.kg-1i.v. (ED50 = 2.9 mg.kg-1i.v.). In acute rat preparation, the low voltage fast waves basal EEG pattern was not modified by tianeptine in a dose range of 1.25 to 20 mg.kg-1i.p. Higher dosage (25 mg.kg-1i.p.) induced high amplitude episodes with few or no delta waves. Low doses which did not apparently modify acute EEG have been tested on sleep-wakefulness cycle in implanted rats. Tianeptine, after single administration, did not modify sleep states up to 2.5 mg.kg-1i.p. An increased wakefulness was observed during the first hour after 5-10 mg.kg-1i.p., afterwards sleep states returned to control values up to 12 h. A subsequent 12 h recording performed 24 h after treatment did not show any change compared to pretreatment baseline. After sub-chronic administration (2.5 mg.kg-1i.p./day, 9 days) no change was observed in sleepwake pattern during or after cessation of treatment. Tianeptine EEG profile is radically different from those usually induced by classical tricyclic antidepressants.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1988

Modified hemipelvectomy: conservation of the upper iliac wing and an anterior musculo-cutaneous flap.

Very large bone and soft tissue tumors located in the pelvis or upper thigh may require hemipelvectomy if local excision is not possible. Classical hemipelvectomy is associated with a high risk of local complications and usually with a poor functional result. This paper describes a modified hemipelvectomy where the preservation of the upper iliac wing provides a counterpressure for the external prosthesis, and a vascularized anterior musculo-cutaneous thigh flap decreases the risk of skin necrosis and wound problems.

Adult↗
PubMed1988

[Peroxidase deficiency in eosinophils: an optical and electron microscopy cytologic study apropos of a case].

A case of eosinophil peroxidase deficiency (EPO), discovered using an automated differential leukocyte cell counter, was studied using optical and ultrastructural cytologic methods. The blood and bone marrow eosinophilic cells had an abnormal ultrastructural aspect with important modifications of the specific granule matrix. No peroxidase activity could be revealed in these cells using optical or ultrastructural techniques. The mechanism and significance of this anomaly raise the question of the physiological function of this enzyme.

Adult↗
PubMed1987

Subrenal capsule assay for fresh human tumors in immunocompetent mice; an inappropriate technique for non-small cell lung cancer.

The subrenal capsule assay (SRA) seems to present some difficulties for the evaluation of the chemosensitivity of antineoplastic agents against fresh tumor xenografts. A study was therefore carried out to verify whether two different xenografts would behave in a similar way. Tumors such as melanoma provided adequate homogeneous material for this technique, while non-small cell lung carcinoma (NSCLC) were heterogeneous since the 1 mm3 specimen grafted under the renal capsule usually contained diffuse areas of necrosis and of infection. Furthermore, a large proportion of the grafted specimens, 257 out of 298, did not contain any tumor at all on microscopic examination even when they showed macroscopic growth. Added to these discrepancies, a random microscopic analysis of 180 adjacent fragments of NSCLC and melanomas demonstrated that the variability of heterogeneous tumors precludes any meaningful comparison between homologous tumor tissues designed to be grafted on treated and on control mice. The anti-inflammatory effect of chemotherapeutic drugs on the host's reaction to the graft is probably responsible for the differences between the macroscopic growth results observed in pieces grafted to both treated and control mice: however, it could not be simulated by hydrocortisone (HC) under our experimental conditions. This allows us to conclude that fresh tumors from NSCLC cannot be used in SRA.

Animals↗
PubMed1987

[The Schilling test in Biermer's disease, problems of false negative reactions. Apropos of a case].

A case of pernicious anemia in a 30 years old men is described. This disease was typical for the hematologic, immunologic and medullary patterns, for his evolution, but the Schilling test, a dual tracer method, did not confirm the diagnosis. The contradictory of this result can be explained wether by the bias of the test itself, or by the intestinal malabsorption due to the vitamin B12 deficiency, or by other factors like bacterial overgrowth state (associated in the pernicious anemia) and a high level of antibodies to intrinsic factor.

Adult↗